The response of cells from the feline somatosensory cortex was investigated with compound multibarrel micropipettes filled with amino acids (D-1-homocysteic acid (DLH), GABA) and penicillin (PCN). Drugs were applied by iontophoresis. Typical unit spikes derived from 0.2mm to 2.0mm of cortex were excited by DLH and inhibited by GABA. Although topical PCN application resulted in classical surface interictal and ictal discharges, cataionic iontophoresis of PCN (100nA) most commonly produced the following responses: 1) Initially a decrease in unit firing rates. 2) Return to the prespiking with longer duration PCN iontophoresis (10-20 min). 3) Development of grouped unit spiking with longer duration PCN iontophoresis (10-20 min). 4) Transient increase in firing rate following the end of PCN iontophoresis. The unit response pattern to PCN was not clearly related to electrode configuration, form, tip size, ejecting current, carrier ions, or pH. Therefore, the iontophoretic characteristics of PCN effecting its release were evaluated.